Isoflavones are polyphenol antioxidants that act as plant hormones. They have a similar structure to human oestrogen and are popular supplements for treating symptoms associated with menopause and pre-menstrual syndrome. Isoflavone supplements may also protect against heart disease, osteoporosis and cancers of the prostate in men, and breast in women.
Dietary isoflavones
Around a thousand different plant isoflavones have been identified, but only five with oestrogen activity are found in significant amounts in our food:
- Genistein, daidzein and glycitein are mainly derived from soy and Japanese Arrowroot ( kudzu)
- Formononetin and biochanin A (which are metabolised to form daidzein and genistein) are obtained from chickpeas, lentils and mung beans.
In Japan, where soy is a dietary staple, intakes of isoflavones are 50mg to 100mg per day for both men and women, compared with typical western intakes of just 2mg to 5mg isoflavones per day. Blood levels of isoflavones in Japan are therefore as much as 110 times higher than those typically found in the West.
Importance of probiotic bacteria
Dietary plant isoflavones are mostly eaten in an inactive form, attached to sugars to form glycosides such as genistin and daidzin. Once ingested, bowel bacteria ferment these sugar-isoflavones to release the active forms (aglycones such as genistein and daidzein).
Isoflavone metabolism varies greatly from person to person, and their absorption is greatest in those with the slowest gut transit time (ie a tendency towards constipation).
Some people also possess probiotic intestinal bacteria (eg Lactobacillus, Bacteroides and Bifidobacterium species) that can metabolise daidzein to a more powerful oestrogen, called equol. In fact, people can be divided into two distinct groups: equol-producers and nonequol producers.
Equol has a higher antioxidant activity than any other isoflavone, and equol producers gain greater health benefits from isoflavones than nonequol producers. This may explain why some studies show benefit from isoflavone supplements while others have not.
It also means that if you are taking isoflavone supplements, it’s a good idea to take a probiotic supplement to boost your levels, or to take a prebiotic oligosaccharide supplement to feed those you already possess.
Isoflavones versus human oestrogens
Compared with oestradiol, the strongest human oestrogen, the action of plant phytoestrogens such as genistein is around 100 times weaker. Even so, isoflavones have a normalising effect on oestrogen status. Isoflavones can stimulate oestrogen receptors to provide a useful oestrogen boost when levels are low at the menopause. Conversely, isoflavones can block the effects of excess human oestrogen by occupying and blocking receptors so they interact less with stronger human oestrogens. Isoflavones also stimulate the production of sex hormone binding globulin (SHBG), which reduces the level of active, free oestrogen in the circulation.
Isoflavones and premenstrual syndrome
A study involving 23 women with premenstrual syndrome found that taking soy protein, providing 68mg per day soy isoflavones significantly reduced headache, breast tenderness, cramps and swelling compared with placebo.
In Japan, a study involving 144 women found that women who were classed as equol producers were 2.3 times less likely to have symptoms of premenstrual syndrome than equol producers.
Isoflavones and menopause
Soy isoflavones are widely used to reduce menopausal hot flushes and night sweats.
The results from 16 studies, involving 1710 women, show that soy isoflavones can reduce hot flashes by 25.2% more than placebo, making them around 45% as effective as prescribed oestradiol overall. Soy isoflavones were slower acting however, taking at least 13 weeks to achieve half their maximal effects, compared with 3 weeks for oestradiol. If you are taking soy isoflavone supplements, they will continue to produce increasing benefit over the course of a year or more, with 80% of their maximal effect achieved by 48 weeks, so don’t give up on them too soon.
Soy and heart disease
Soy isoflavones can reduce the risk of coronary heart disease in a number of ways. As well as having antioxidant, anti-inflammatory actions, isoflavones interact with oestrogen receptors within the circulation to dilate coronary arteries, reduce arterial stiffness, lower blood pressure and reduce blood stickiness to discourage unwanted blood clots.
Good intakes of soya foods can significantly reduce total and ‘bad’ LDL-cholesterol levels and triglycerides while significantly increasing ‘good’ HDL-cholesterol. Those with raised cholesterol levels gained the most benefit. The results from 17 studies, involving over 17,200 cardiovascular disease events found that those with the highest soy intake were around 17% less likely to experience a heart attack or stroke than those with low intakes.
Although a lot of research involves postmenopausal women, a study involving 61 Scottish males (aged 45 to 59) found that increasing isoflavone intake for just 5 weeks produced significant reductions in blood pressure and LDL-cholesterol – even compared with an olive-oil placebo. Significant increases in high-density lipoprotein cholesterol were also observed. The researchers concluded that increasing the dietary content of soy protein (at least 20g) and isoflavones (at least 80mg) would be effective for reducing heart disease risk among high-risk, middle-aged men, too.
Some studies have not found links between isoflavone intakes and cardiovascular disease, however, which may be due to the equol status of those taking part.
Isoflavones and osteoporosis
Isoflavones mimic the effects of natural oestrogen on bones and, in theory, should increase the activity of bone-building cells, and reduce the activity of bone-dissolving cells, too. This is the case, with studies showing that soy isoflavones significantly increased bone mineral density by 54% compared with placebo, and decreased the bone resorption markers by 23% in women taking doses above 75 mg per day.
Taking soy isoflavones may therefore help to protect against postmenopausal osteoporosis.
Isoflavones and memory
Consuming a high soy diet improves memory and thought processes in young healthy students (both male and female) and in postmenopausal women. In a study involving 33 postmenopausal women who were not on hormone replacement therapy, those taking isoflavones for 12 weeks showed significantly greater improvements in memory recall, sustained attention tasks, learning rule reversals, and in planning tasks than those taking placebo.
Isoflavones and prostate cancer protection
Soy isoflavones may offer men some protection against prostate cancer. Urologists have found that even in men at risk, taking soy isoflavones reduced the chance of a prostate cancer diagnosis by 51% and had a good safety profile.
Isoflavones and breast cancer protection
The results from 35 studies suggest that soy isoflavones have a protective effect against breast cancer for both pre-menopausal and post-menopausal women, but the effect is stronger in Asian women which may relate to their equol status. In Asian countries, those with the highest soy isoflavone intake were 41% less likely to develop breast cancer than those with the lowest intakes, for both premenopausal and postmenopausal women. For postmenopausal women in Western countries, soy isoflavone intake was associated with an 8% lower risk of breast cancer.
There is a growing recognition that women with a history of breast cancer may benefit from soy isoflavones.
A study that followed almost 2000 women who were breast cancer survivors for 6 years stated that: ‘Soy isoflavones consumed at levels comparable to those in Asian populations may reduce the risk of breast cancer recurrent in women receiving tamoxifen therapy, and that supplements appear not to interfere with tamoxifen efficacy’.
This was recently confirmed in a study that enrolled 6,235 women with breast cancer and followed them for over 9 years. Those with the highest intake of dietary isoflavones (1.5mg or more daily)were 21% less likely to die, from any medical cause, during the follow-up than those with the lowest dietary isoflavone intakes (less than 0.3mg per day).
The American Institute for Cancer Research (AICR) have also stated that soy is safe for breast cancer patients and survivors.
Red clover isoflavones
Red clover isoflavones are not naturally found in the diet, but contain similar isoflavones to those present in soy, and are used in supplements to treat menopausal symptoms. The results from five studies suggest that women who take supplements providing 80mg red clover isoflavones per day experienced an average of 3.6 fewer menopausal hot flushes per day than those taking placebo.
Isoflavones dose
A typical dose for soy isoflavones is 40mg to 100mg isoflavones a day. For best effect, doses of at least 75mg are recommended.
For products containing soy protein, 60g of soy protein provides 45mg isoflavones.
Isoflavones safety
If you have a history of breast (or prostate) cancer, always follow your own doctor’s advice about whether or not to take isoflavone supplements.
Image credit: buyonego/flickr;
